Existing detectors used by the pharmaceutical industry to conduct High Performance Liquid Chromatography (HPLC) measurement during drug discovery and development exhibit a number of limitations. This project will focus on developing a next-generation detector, a Condensation Nucleation Light Scattering Detector (CNLSD), to overcome these limitations. In addition to its uses in the pharmaceutical industry, CNLSD technology will advance the pace of innovation in multiple industrial, government and academic settings by substantially reducing the cost of extremely high-performance chemical composition measurement. UV detectors are the HPLC detector of choice in the pharmaceutical industry today because they are inexpensive, have excellent low-level detection and a linear response. However, on the frequent occasions when chromophores are missing from the compound of interest, alternative HPLC detectors must be used. These detectors are primarily Evaporative Light Scattering Detectors (ELSD) or Mass Spectrometry (MS). ELSD technology is limited however, having inadequate sensitivity, poor linearity and poor universality when compared with UV detectors. MS does not exhibit these limitations, but is expensive and difficult to use. CNLSD will be the much-needed, low cost yet high performance, improved HPLC detector, providing lower detection levels, better linearity and better universality than existing detectors at a relatively low cost. A prototype CNLSD, developed and evaluated with SBIR funding in Phase 1, showed excellent test results for metal ions, biogenic amines, carbohydrates, and lipids, including good low level detection and linearity over several orders of magnitude. These results were presented to analytical chemists in site visits to three major pharmaceutical companies. All were excited by the promise shown by this new technology and, dependent upon successful Phase 2 commercialization, all three companies have included CNLSD in their 2005/2006 capital equipment budgets. Under Phase 2 funding, a second prototype CNLSD will be built. The Phase 2 prototype will incorporate an innovative, water-based CPC (WCPC), only recently made commercially available. Theoretical research shows that the WCPC should improve the sensitivity of CNLSD beyond that of the Phase 1 prototype built using an alcohol-based CPC. In Phase 2, using Phase 1 test protocols, the improved CNLSD will be evaluated to ensure that the use of the WCPC has improved the sensitivity as predicted. After evaluation, the Phase 2 prototype will be further refined and Phase 2 funding will be used to build five beta CNLSD units rugged enough to be evaluated in situ by partners in the pharmaceutical industry. Finally, in Phase 3, a commercially viable, rugged CNLSD will be manufactured for sale.